DNA damage modulates nucleolar interaction of the Werner protein with the AAA ATPase p97/VCP.

We report a novel nucleolar interaction between the AAA ATPase p97/VCP and the Werner protein (WRNp), a member of the RecQ helicase family. p97/VCP mediates several important cellular functions in eucaryotic cells, including membrane fusion of the endoplasmic reticulum and Golgi and ubiquitin-dependent protein degradation. Mutations in the WRN gene ...
cause Werner syndrome, a genetic disorder characterized by premature onset of aging symptoms, a higher incidence of cancer, and a high susceptibility to DNA damage caused by topoisomerase inhibitors. We observed that both WRNp and valosin-containing protein (VCP) were present in the nucleoplasm and in nucleolar foci in mammalian cells and that WRNp and p97/VCP physically interacted in the nucleoli. Importantly, the nucleolar WRNp/VCP complex was dissociated by treatment with camptothecin, an inhibitor of topoisomerase I, whereas other WRNp-associated protein complexes, such as WRNp/Ku 80, were not dissociated by this drug. Because WRN syndrome cells are sensitive to topoisomerase inhibitors, these observations suggest that the VCP/WRNp interaction plays an important role in WRN biology. We propose a novel role for VCP in the DNA damage response pathway through modulation of WRNp availability.
Mesh Terms:
Adenosine Triphosphatases, Animals, Antigens, Nuclear, Camptothecin, Cell Cycle Proteins, Cell Nucleolus, Cells, Cultured, Cloning, Molecular, DNA Damage, DNA Helicases, DNA Topoisomerases, Type I, DNA-Binding Proteins, Endoplasmic Reticulum, Exodeoxyribonucleases, Fluorescent Antibody Technique, Golgi Apparatus, Humans, K562 Cells, Membrane Fusion, Mice, Mutation, Protein Binding, Protein Structure, Tertiary, RecQ Helicases, Werner Syndrome
Mol. Biol. Cell
Date: Oct. 01, 2003
Download Curated Data For This Publication
138430
Switch View:
  • Interactions 4